Mast cells in liver disease progression: an update on current studies and implications

Mast cells (MCs) are innate immune cells originating from CD34+/C D117+ hematopoietic stem cells and regulate liver disease progression.[1] With a variety of surface receptors, MC activation is triggered by two main receptor-dependent pathways: IgE/high-affinity receptor for the Fc region of IgE (FcεRI) and IL-33/sup-pressor of tumorigenicity 2 (ST2).[2] Upon liver damage, MCs degranulate releasing mediators, including pre-formed bioactive metabolites (histamine, tryptase, and chymase), newly synthesized cytokines (TGF-β, TNF-α, and I L- 1β), and de novo lipid mediators (leukotriene B4, leukotriene D4, prostaglandin)[3] (Figure 1). TGF-β1, TNF-α, IL-6, IL-10, and synaptophysin 9 (SYP-9) are re-leased upon liver damage by paracrine interactions be-tween MCs and hepatocytes (through TGF-β,[4] TNF-α[5]), cholangiocytes (through IL-10, TGF-β[6]), HSCs (through SYP- 9, TGF-β1[7]), and Kupffer cells (through TNF-α, I L- 6[8 ]). This review encompasses the most recent stud-ies involving MCs, their mediators, and the impact on liver disease.